Reduced bone mineral density in men following chemotherapy for Hodgkin's disease

Abstract

(Finkelstein et al., 1992). Men who undergo bilateral orchidectomy have a rapid and progressive loss of lumbar spine integral bone with time from orchidectomy (Stepan et al., 1989). In men with hyperprolactinaemic hypogonadism restoration of normal testicular function is assocated with a significant increase in cortical BMD (Greenspan et al., 1986). Siilarly, restoration of normal serum testosterone in men with idiopathic hypogonadotrophic hypogonadism is also associated with a significant increase in cortical BMD (Finkelstein et al., 1989 puted tomography. There was, however, a significant reduction in cortical and trabecular BMD in women with chemotherapy-induced premature ovarian failure compared with similarly treated women with normal ovarian function.We have studied BMD in 29 men in complete remission following treatment of Hodgkin's disease. We have studied the relationship between serum testosterone and BMD, and the effect on BMD of time elapsed since completion of chemotherapy, type of chemotherapy received and number of cycles of chemotherapy. S and methodsWe studied 29 caucasian men who had previously received chemotherapy for Hodg9in's disease. The study subjects were drawn from 50 consecutive men who presented to the Medical Oncology Dertment at Christie Hospital with newly diagosed Hodgkin's diseas and who were randomised to receive MVPP or hybrid chemotherapy. The 50 men took part in a study investigating the effects of MVPP and hybrid chemotherapy on gonadal function, and 29 of these men consented to have measurements of BMD performed. In the 29 men who underwent measurements of BMD, age at onset of chemotherapy was 31.0 ± 1.9 (mean + standard error, range 16.4-54.0) years. Twelve men had received a mean of 7.5 (range 5-8) cycles of MVPP (mustine 10 mg i.v. and vinblasin 10 mg i.v. on days 1 and 8 with procarbazine 150 mg daily and prednisolone 50 mg daily on days 1-14 of a 42 day cycle) and 17 men had received a mean of 7.5 (range 6-8) cycles of hybrid chemotherapy (vinblastine lOmgi.v. on day 1, with chlorambucil 1Omg daily, procarbazine 150 mg daily and prednisolone 50 mg daily on days 1-7, and etoposide 200mg m-2 i.v., viris 2 mg i.v. and doxorubicin 50 mg m-2i.v. on day 8 of a 28 day cycle). Twenty-four men received radiotherapy (15 to chest and mediastinum, eight to neck and one to axilla) but none in a radiation field which included the testes or the parts of the skeleton studied. All men were in complete remission at the time of study, and all had azoospermia.Blood samples were taken for estimation of serum testosterone, sex hormone-binding globulin (SHBG), LH and FSH. Seven men had blood samples taken on one occasion, 19 on two occasions and three on three occasions. There were therefore a total of 54 blood samples taken 2.7 ± 0.2

Bone tissue as the site of action of oncological drugs

“…This is confirmed by studies conducted on patients treated for Hodgkin's lymphoma -there has been observed a statistically significant reduction in the density of trabecular and cortical bone in cases of ovarian failure, as compared with patients retaining normal ovarian function [27,28]. The effects of chemotherapy on gonads have also been implicated in the reduction of BMD in males treated for the same condition, as suggested by the correlation between BMD and testosterone levels [29]. Impaired gonad function occurred more often in patients treated for Hodgkin's lymphoma as compared with the group with non-Hodgkin's lymphoma, due to the difference in the frequency of radiation therapy and procarbazine use [30] -however, reduced BMD is also found in females treated for non-Hodgkin's lymphoma.…”

Effect of Chemotherapy on Skeletal Health in Male Survivors from Testicular Cancer and Lymphoma

“…Although, Holmes et al (19) showed small reductions in BMD of the spine, hip, and forearm in 29 men treated with combination chemotherapy for Hodgkin's lymphoma compared with age-matched male controls, endocrine causes were not clearly excluded. Howell et al (24) showed significant reduction in BMD in a group of 36 men who had received procarbazine-containing chemotherapy or high-dose chemotherapy for hematologic malignancy.…”

“…The study by Holmes et al (19) in lymphoma patients was used to determine the numbers of patients required. This study found deviations of BMD in terms of SDs below the mean of agematched males (Z-scores) of À0.8 at the radius, À0.6 at the lumbar spine, and À0.4 at the femoral neck.…”

Bone mineral density in patients undergoing bone marrow transplantation for myeloid malignancies

“…There are reports of decreased bone mineral density in long-term survivors of Hodgkin's disease, both men 18 and women, 19,20 with possible causes being treatment-related hypogonadism, direct effect of chemotherapy on bone, or an effect of high-dose glucocorticoid on bone. Osteoporosis and vertebral fractures may occur in children with newly diagnosed acute lymphoblastic leukemia and following its treatment.…”